Molecular mechanisms linking obesity, diabetes, and cancer

Abstract

The past few years have provided substantial evidence for the vital role of the local tumor microenvironment for various aspects of tumor progression. With obesity and its pathophysiological sequelae still on the rise, the adipocyte is increasingly moving center stage in the context of tumor stroma-related studies. To date, we have limited insight into how the systemic metabolic changes associated with obesity and the concomitant modification of the paracrine and endocrine panel of stromal adipocyte-derived secretory products (“adipokines”) influence the incidence and progression of obesity-related cancers. Here, we discuss the role of extracellular matrix proteins, Type VI collagen and its cleavage peptide endotrophin, associated with obesity and its potential impact on cancer biology. Furthermore, a number of cancers such as pancreatic, liver, breast, and female reproductive cancers have shown an increased prevalence and a higher mortality rate in patients with diabetes compared to healthy subjects, suggesting an association between diabetes, especially type 2 diabetes and cancer incidence and progression. We discuss our current understanding how diabetes mellitus and cancer risk may be linked, and what the implications are for the treatment of diabetic cancer patients, particularly with a focus on hyperglycemic memory effects in cancer cells.